Rosacea is a chronic dermatological condition characterized by flushing, erythema, papules, pustules, inflammatory nodules and telangiectasia. Although disease etiology remains unclear, skin inflammation has been identified as the main contributor to disease pathology. Isoprenylcysteine (IPC) analogs represent a novel class of topical anti-inflammatory compounds being developed as therapeutic agents for rosacea. As part of the Phase II SBIR project, Signum identified a lead investigational new drug (IND)-candidate, SIG990 which demonstrated strong efficacy in in vitro and in vivo models. Through pharmacokinetic and safety pharmacology studies, the preclinical safety profile for SIG990 was established. In the renewal application, we propose to continue SIG990's development path towards clinical application and FDA approval by conducting further safety assessment of drug product toxicity. Upon completion of the proposed aims, Signum will enter SIG990 into the Phase III clinical trials. PUBLIC HEALTH RELEVANCE: Rosacea is a common, chronic skin disorder afflicting people all around the world, including ~16 million Americans. Currently available treatments have yielded mixed results, often leaving patients with significant levels of facial redness and inflammatory lesions. Successful pharmaceutical development of topical IPC analog anti-inflammatories will provide an important additional, and potentially better, therapeutic option for people suffering from rosacea associated redness.